Synthetic 3D extracellular matrices (ECMs) find application in cell studies, regenerative medicine, and drug discovery. While cells cultured in a monolayer may exhibit unnatural behavior and develop very different phenotypes and genotypes than in vivo, great efforts in materials chemistry have been devoted to reproducing in vitro behavior in in vivo cell microenvironments. This requires fine-tuning the biochemical and structural actors in synthetic ECMs. This review will present the fundamentals of the ECM, cover the chemical and structural features of the scaffolds used to generate ECM mimics, discuss the nature of the signaling biomolecules required and exploited to generate bioresponsive cell microenvironments able to induce a specific cell fate, and highlight the synthetic strategies involved in creating functional 3D ECM mimics.

Glycans have been selected by nature for both structural and 'recognition' purposes. Taking inspiration from nature, nanomedicine exploits glycans not only as structural constituents of nanoparticles and nanostructured biomaterials but also as selective interactors of such glyco-nanotools. Surface glycosylation of nanoparticles finds application in targeting specific cells, whereas recent findings give evidence that the glycan content of cell microenvironment is able to induce the cell fate. This review will highlight the role of glycans in nanomedicine, schematizing the different uses and roles in drug-delivery systems and in biomaterials for regenerative medicine.

The generation of 3D-bioprintable and biocompatible hydrogels based on elastin and hyaluronic acid is described. The procedure is based on a biocompatible click reaction between maleimide and thiol for the final crosslinking, employable with living cells due to fast kinetics and absence of side products. To this end, both α-elastin and hyaluronic acid were functionalized with linkers ending with maleimide groups, at controlled functionalization intensities, and crosslinked with a dithiolÀ PEG linker. Varying the equivalents of the three reagents, four different hydrogels were obtained and their biocompatibility, swelling capacity and printability were tested. Biological experiments were performed with human lung fibroblast, human bronchial epithelial and human endothelial cell lines cultured in the hydrogels. Fibroblasts and epithelial cells can survive and proliferate. Epithelial cells showed an increased expression of CD44 and integrin α v β 3. Gene expression analysis revealed up-regulation of metalloproteinases both in normal fibroblast and epithelial cells.